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ASCO 2022: Novel CAR T-Cell Therapy Targets CD20 in Treatment of B-Cell Malignancies

By: Vanessa A. Carter, BS
Posted: Wednesday, June 29, 2022

Saatva Swarup Neelapu, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues assessed the first-in-class allogeneic gamma delta chimeric antigen receptor (CAR) T-cell therapy ADI-001 in patients with B-cell malignancies. Presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 7509), the results of this phase I trial “suggest the potential for off-the-shelf gamma delta CAR T-cell therapy to be an effective treatment possibility for patients with B-cell lymphoma,” said Dr. Neelapu in an MD Anderson press release.

“ADI-001 also has both adaptive and innate cytotoxic effector functions to complement CAR targeting, potentially enhancing efficacy and reducing the possibility of tumor escape due to antigen loss,” stated the investigators. “ADI-001 expresses major histocompatibility complex-independent gamma delta T-cell receptors, thus lowering the risk of graft-versus-host disease without the need for gene-editing.”

This study enrolled eight patients with relapsed or refractory advanced B-cell malignancies who received more than two prior systemic therapies and demonstrated CD20 expression. Participants received conditioning therapy with cyclophosphamide and fludarabine, as well as ADI-001 in three flat dose levels in a 3 + 3 dose-escalation design.

A total of six patients were evaluable for analysis, five with large B-cell lymphoma and one with mantle cell lymphoma. The median number of prior therapies was 3.5, and one patient received prior anti-CD19 CAR T-cell therapy. Dose levels 1 and 2 were received by three participants each.

Although most adverse events were of grade 1 or 2, adverse events of special interest included cytokine-release syndrome and immune effector cell–associated neurotoxicity syndrome. Of note, graft-versus-host disease and protocol-defined dose-limiting toxicity events did not appear to occur. The objective response rate and complete response rates were both 67% at day 28, and both individuals who had more than a 3-month posttreatment follow-up remained in complete response.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.


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